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Vitellogenin and Common Ancestry: Understanding synteny

This post is the second in this series. The first is here. In this post, we explore the concept of “shared synteny” and see how it was used to find vitellogenin gene fragments in the human genome.

In C.S. Lewis’s book Prince Caspian, the Pevensie children find themselves, upon their unexpected return to Narnia, in the ruins of their former palace, Cair Paravel. Unaware that they are several hundred years beyond “their time” as kings and queens as recounted in The Lion, the Witch, and the Wardrobe, they at first do not recognize the ruins. Over time, however, they begin to notice similarities. Though Cair Paravel was not on an island, nor was an apple orchard planted up to the walls, there were too many similarities to ignore. The great hall, with its dais, was the correct size and shape, though now roofless. The well was in the correct location, and also the correct shape. Near the well, Susan had found a gold chess piece, exactly alike to the ones they remembered using. Though at first difficult to imagine, more and more pieces fit into place, strengthening their conviction that they are, in fact, in the ruins of their once glorious home. As they begin to “see” it as it was, Lucy hits upon an idea that will settle the matter readily:

‘There’s one thing,’ said Lucy. ‘If this is Cair Paravel there ought to be a door at the end of this dais. In fact we ought to be sitting with our backs against it at this moment. You know – the door that led down to the treasure chamber.’

‘I suppose there isn’t a door,’ said Peter, getting up. The wall behind them was a mass of ivy.

‘We can soon find out,’ said Edmund…

-C.S.Lewis, Prince Caspian

As those who have read the story know, the children soon discover beyond doubt that they are indeed in the ruins of Cair Paravel: they find the treasure chamber, and within it the gifts that Aslan had given them hundreds of years before.

The reason that Cair Paravel remained recognizable, even after hundreds of years, was that several of its features were resistant to the effects of long spans of time. Though the original peninsula could become an island, an orchard overgrow, and a roof fall in, other features would not shift: the shape, size, and relative placement of the walls and rooms persisted.

Like buildings, the DNA sequences in an organism’s genome can retain features for very long spans of time even after their original function is lost. These features can be used to make predictions about what we should find, and where. One such feature is the organization of genes along a chromosome. For example, consider two closely related species. Since these species recently shared a common ancestral population, and thus the same genome, we would expect the majority of genes in these two species to remain in the same locations relative to each other (Figure 1):

Figure 1. Closely related species have not only highly similar genes and inter-gene sequences, but have their genes conserved in the same spatial arrangement: in other words, they have large blocks of genes with shared synteny.

This conserved gene order along chromosomes is known as shared synteny: “syn” here means “together” and “teny” means “held”, so “synteny” means “held together” – genes held together in the same pattern in related organisms. Genes in closely related organisms can be present in blocks of synteny that are thousands of genes long. Over time, gene order can be rearranged through chromosome breakage and rejoining – slowly erasing shared synteny in separate lineages. Despite these processes, however, shared synteny can persist for a very long time in distantly related species. Like the ruins of Cair Paravel, it takes a long time to remove the overall pattern to the point where it is not recognizable.

Going on an egg hunt

The knowledge that shared synteny can persist in separate lineages for a very long time was useful when looking for vitellogenin gene fragments in the human genome. As we saw in Part 1 of this series, placental mammals do not require vitellogenin genes to supply their embryos with yolk. Converging lines of evidence, however, indicate that placental mammals are the descendants of egg-laying ancestors. For example, placental mammals and birds (a group of modern-day, egg-laying organisms) are thought to have shared a common ancestral population about 310 million years ago. If this is the case, then it is possible that vitellogenin gene sequences, however fragmentary, might remain in the human genome. The scientists interested in this question used synteny to find the regions of the human genome worth examining.

Modern birds (such as chickens) have three vitellogenin genes: VIT1, VIT2, and VIT3. The latter ones sit side by side in the chicken genome, with VIT1 in a different location. The three VIT genes sit next to other genes in the chicken genome: VIT1 sits next to a gene called “ELTD1”, and VIT2 and VIT3 sit between genes named “SSX2IP” and “CTBS”. These genes are not involved in making egg yolk - they just happen to be the closest neighbors of the VIT genes (Figure 2):

Figure 2. The genomic context for the three VIT genes in chicken.

With these data in hand, the researchers then searched the human genome for the genes near to the chicken VIT genes. These three genes (ELTD1, SSX2IP, and CTBS) are also found as functional genes in humans - and as expected, these genes have the same spatial arrangement in the human genome as they do in chickens (Figure 3):

Figure 3. The genes flanking the VIT genes in chicken are present in the human genome in the same spatial pattern.

The researchers then did a careful sequence comparison between these regions in the human and chicken genomes. The gene sequences for ELTD1, SSX2IP, and CTBS were already known to be highly similar, but they found that other sequences in this region matched as well. We can represent sequence matches between the two genomes as a black bar between them to show what they found (Figure 4):

Figure 4. Shared synteny between humans and chickens spanning the regions with functional chicken VIT genes. Black bars between the two chromosomes indicate sequence matches. This figure is based on data from Brawand et al., 2008.

What is important to note is that not only did the researchers find fragmentary remains of all three VIT genes in the human genome (though the human VIT1 sequence was the best preserved of the three) they also found sequence matches that span both regions on either side of the genes in question. This evidence increases our confidence that we are indeed looking at regions with shared synteny: in other words, a region in two present-day species that was once a region in the genome of their common ancestral population. The human VIT sequences, as expected, are far too fragmentary to act as functional VIT genes.

In the next post in this series, we’ll begin to explore how Jeffery Tomkins examines this evidence in his attempt to refute it.

See links on sidebar for some articles from BioLogos related to this topic.

About the Author

Dennis Venema is professor of biology at Trinity Western University in Langley, British Columbia and Fellow of Biology for BioLogos. He holds a B.Sc. (with Honors) from the University of British Columbia (1996), and received his Ph.D. from the University of British Columbia in 2003. His research is focused on the genetics of pattern formation and signaling using the common fruit fly Drosophila melanogaster as a model organism. Dennis is a gifted thinker and writer on matters of science and faith, but also an award-winning biology teacher—he won the 2008 College Biology Teaching Award from the National Association of Biology Teachers. He and his family enjoy numerous outdoor activities that the Canadian Pacific coast region has to offer.

"What kind of evidence would somebody need to have in order to be rationally compelled to say that an event was a miracle? That person would have to know that this event could not possibly be explained by future science. But not only is such a belief unwarranted, it’s also bad for future science to believe it."

These provocative words are written by Princeton philosopher Hans Halvorson (a Christian), in an article that itself provoked some good discussion when we posted it last week.

Check out the full article (link in comments), and then respond to the quote above. Does calling something a "miracle" put it in danger of being debunked by future scientific advances? Is there a different way of thinking about the concept of a miracle, that might satisfy his concerns? Feel free to discuss below. ... See moreSee less

Hard for me to see that the Incarnation is not a miracle. For others , God could be working on a quantum level?? But does the latter fall into”God of the Gaps?”

5 hours ago · 1

Amen🌀 Jesus doesn't care about Alabama Crimson Tide 🏈 football. Instead, He loves 🌀 Spring and the start of ⚾ baseball season. That's why He started His own story, "In the Big inning..." Just watch 🌀 His wind-up! You need to start reading your 📖 Bible!

3 hours ago

One thing for sure, it is more a philosophical question than a religious one.

7 hours ago · 2

Great article. In answer to you question about a different way of thinking about miracles that would "satisfy his concern", to me it would make sense to explain a miracle in terms of something that everyone (religious and non-religious alike) would have no explanation for, given our current understanding of science.

Science will never describe the full expanse of reality. Science is not geared to that end. This is basic knowledge.
Reason is the handmaiden of faith because faith takes us where reason cannot go. As such, the only thing that will ever describe the fill expanse of reality is faith supernaturally given by God, i.e. God graciously enlightening the intellect. Reason gives way to faith because reason is limited in its capacity to describe reality.
This is not to say reason is not essential. It is the handmaiden of faith because it is a true and good servant to faith. As such faith and reason never contradict, but faith does transcend reason.

10 hours ago · 5

I'm tired of these types of questions constantly being proposed. It was not a scientist who discovered that dead human beings do not rise from the dead (which is different than Jesus resurrection) it was simple human experience. Therefore, the question is rather silly to ask. My first reply is to ask: who cares if Jesus resurrection contradicts science? My second reply is to make the observation that this question is phrased in such a way that science is presupposed as the final arbiter of truth claims like the resurrection of Jesus. Thirdly, how exactly could scientists study the resurrection of Jesus? Scripture tells us that God raised Jesus from the dead. Can science study this claim? Fourth, it would be one thing to subject the resurrection to some sort of scientific investigation ( I know not what or how) and a completely different thing to study what the resurrection of Jesus means for me or you personally. It seems Biologos is in need of some good theologians and philosophers to add to this conversation. Finally, this question smacks of a form of Evidentialism that would make faith subject to the vagarities of evidence. In the end I have to affirm that it matters little to me if the resurrection of Jesus did contradict science. On another note, one could ask: whose "science" and which scientists?

3 hours ago · 1

Exactly so.

11 hours ago · 1

Mmmmmm, I would say that a resurrection is contradictory to observed evidence, but that's fine. A God that is truly supernatural would act supernaturally at times. Although, I suppose God could whip up a truly natural Star Trek hypospray to overcome the decay process and relaunch the body's systems.